Phage display is an extraordinarily powerful and versatile technology that enables the selection of novel binding functions from large populations of randomly generated peptide sequences. From a sufficiently complex library, phage bearing peptides with practically any desired binding activity can be physically isolated by affinity selection, and, since each particle carries in its genome the genetic information for its own replication, the selectants can be amplified in bacteria. This aim of this project is to develop a new platform for peptide display on virus-like particles (VLPs) of the RNA bacteriophage MS2. We envision several applications for the MS2 VLP, but we wish especially to emphasize its utility for vaccine development. It will integrate into a single platform the potent immunogenicity of a VLP with the affinity selection capability of conventional phage display. Filamentous phages are now the most widely used vehicles for phage display, and provide an efficient means for epitope identification. However, the peptides they display are typically poorly immunogenic, because they do not normally support the formation of dense repetitive arrays. Meanwhile, other VLP systems permit engineered display of specfic pre-selected epitopes, but are incapable of peptide library display and affinity selection. We think MS2 VLPs will overcome these limitations. Peptides displayed on MS2 VLPs are strongly immunogenic, and can be engineered to encapsidate the same mRNA molecule that encodes them, thus enabling recovery of affinity selected sequences by RT-PCR. Further, the comparative simplicity of MS2 VLP structure and assembly makes it possible to conduct the entire iterative selection/amplification process in vitro. This could make it easier to achieve high library complexities, and should make automation possible. PUBLIC HEALTH RELEVANCE: This project aims to develop a new platform for peptide display using virus-like particles of bacteriophage MS2. Several applications are envisioned, but because of their potent immunogenicity, these particles should be especially useful for vaccine discovery.